Can Sebum be Used as a Diagnostic Biofluid for Parkinson’s Disease?
Metabolomics offers unique hope in the battle against Parkinson’s disease through a simple skin swab.
Parkinson’s disease is a degenerative brain condition that affects over 6 million people globally, second only in prevalence to Alzheimer’s disease1. Currently, there is no definitive diagnostic test for Parkinson’s disease, but recent evidence suggests that sebum biomarkers could provide a non-invasive solution for an early detection of the disease.
Changes in the skin are common symptoms of Parkinson’s disease reported in up to 60% of people with Parkinson’s2. Many people with Parkinson’s develop oily skin, known as seborrhea, as a result of an overproduction of sebum3. Alterations in the sebum composition have been studied in relation to acne and other skin disorders, however, sebum as a biofluid has rarely been used in disease diagnostics.
Targeted Assays at Metabolon
Metabolon’s mass spectrometry-based targeted assays provide precise measurements of metabolites in a wide variety of sample matrices. Assays can be customized based on the sponsor’s needs and developed and validated for research use only (RUO) or under Good Clinical Practice (GCP). In addition to custom assay development and validation, sponsors can select from an ever-expanding set of >250 pre-developed assays or one of our discrete panels focused around related biomarkers such as our Sebum Lipid Panel.
A 2019 study reported that the sebum-rich skin of Parkinson’s subjects can capture and retain volatile hydrophobic metabolites that contribute to the musky odor exuding from Parkinson’s patients4. Such alterations in sebum composition may not only reflect a change in skin physiology, but also an altered skin microflora and microbial activity in Parkinson’s patients.
A more recent study from the same research group, published in Nature Communications, reports that sebum obtained from a simple skin swab can be used to help diagnose people with Parkinson’s based on the patient’s pattern of skin lipids and related-metabolites5. Specific lipid pathways that appear to be dysregulated in the skin of Parkinson’s patients, such as sphingolipids and acylcarnitines, have been previously reported to be altered also in patients’ plasma6,7. This evidence suggests that systemic perturbations in lysosomal and mitochondrial metabolism may occur in Parkinson’s and play a role in the pathogenesis of the disease.
The use of sebum as a diagnostic biofluid for Parkinson’s provides the prospect of developing a non-invasive test to perform routine and large-scale screenings for early detection of the disease. Metabolon offers a proven set of solutions to discover and validate biomarkers present in sebum, including a global metabolomics assay and a specific sebum lipid panel, which captures the unique complex lipid composition and fatty acid constituents of sebum. Metabolomic assays and panels created and validated by Metabolon could be used to assist in the development of a non-invasive and inexpensive test to detect the onset of Parkinson’s disease, which may contribute to improved patient outcomes by slowing disease progression.
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What is Sebum?
Sebum is a protective oily substance secreted by mature sebocytes onto the surface of skin to provide waterproofing, thermoregulation and photoprotection as well as antimicrobial activities8,9. Sebum is enriched with an unusual mix of lipid classes that is remarkably different in quantity and quality from lipids found in other organs. Major components are triglycerides, wax esters, squalene and free fatty acids. The fatty acid composition of the complex lipids and the free fatty acid fraction is unique to human skin. Large amounts of the unusual sapienic acid (16:1n10) as well as a variety of odd and branched chain fatty acids are present.
1. Dorsey, E. R. et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology 17, 939-953 (2018).
2. Ravn, A.-H., Thyssen, J. P. & Egeberg, A. Skin disorders in Parkinson’s disease: potential biomarkers and risk factors. Clinical, cosmetic and investigational dermatology 10, 87 (2017).
3. Mastrolonardo, M., Diaferio, A. & Logroscino, G. Seborrheic dermatitis, increased sebum excretion, and Parkinson’s disease: a survey of (im) possible links. Medical Hypotheses 60, 907-911 (2003).
4. Trivedi, D. K. et al. Discovery of volatile biomarkers of Parkinson’s disease from sebum. ACS central science 5, 599-606 (2019).
5. Sinclair, E. et al. Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease. Nature communications 12, 1592, doi:10.1038/s41467-021-21669-4 (2021).
6. Mielke, M. M. et al. Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson’s disease and associated with cognitive impairment: a pilot study. PloS one 8, e73094 (2013).
7. Saiki, S. et al. Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson’s disease. Scientific reports 7, 1-15 (2017).
8. Picardo, M., Ottaviani, M., Camera, E. & Mastrofrancesco, A. Sebaceous gland lipids. Dermato-endocrinology 1, 68-71 (2009).
9. Lovászi, M., Szegedi, A., Zouboulis, C. C. & Törőcsik, D. Sebaceous-immunobiology is orchestrated by sebum lipids. Dermato-endocrinology 9, e1375636 (2017).